Synthesis, evaluation and mechanism exploration of 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors
Synthesis, evaluation and mechanism exploration of 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors
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新型脲酶抑制剂2-(N-(3-硝基苯基)-N-苯磺酰基)氨基乙酰异羟肟酸的合成、评价及机理探索
DOI：
10.1016/j.bmcl.2022.129043
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发表时间：
2022
影响因子：
2.7
通讯作者：
Hai-Liang Zhu
中科院分区：
文献类型：
--
作者：
Wan-Qing Song;Mei-Ling Liu;Liang-Chao Yuan;Su-Ya Li;Yi-Ning Wang;Zhu-Ping Xiao;Hai-Liang Zhu
Abstract Thirteen 2-(N-(3-nitrophenyl)-N-phenylsulfonyl) aminoacetohydroxamic acids which were reported for the first time were designed and synthesized as novel urease inhibitors. Most of them showed higher potency than the positive control acetohydroxamic acid, with 2-(N-(3-nitrophenyl)-N-(4-bromophenylsulfonyl) aminoacetohydroxamic acid (d7) being the most active (IC 50= 0.13±0.01 μM). Compound d7 reversibly inhibits urease with mixed mechanism showing excellent binding affinity to urease active site (K D= 0.34 nM, K i= 0.065±0.003 µM and K i′= 1.20±0.09 µM) and very low cytotoxicity against mammalian cells (cell viability of 91.4% against HepG2 at 250 μg/mL). These positive results indicated that d7 may be used as the lead for further research to develop urease inhibitors with promising properties.
